functionality
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Poznatky o lokálním vzniku, vazbě na jaderné receptory a místním tkáňovém působení kalcitriolu vedly k poznání jeho endokrinních mikrosystémů. Jejich uplatnění u rostoucího organizmu a celoživotní funkčnost představují možnou prevenci a léčbu mnoha onemocnění především přirozenou cestou s minimálními léčebnými náklady.
New findings regarding the local synthesis of calcitriol, its binding on nuclear receptors and its regional tissue effects have led to discovery of its endocrine microsystems. Their application in growing organisms and their lifelong functionality provide possible preventive and treatment modalities in multiple ailments, mostly by natural and minimally expensive means.
- Klíčová slova
- děti, faktory saturace, denní potřeba cholekalciferolu, suplementace,
- MeSH
- financování organizované MeSH
- kalcitriol fyziologie nedostatek MeSH
- lidé MeSH
- nedostatek vitaminu D komplikace patofyziologie MeSH
- receptory kalcitriolu fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: MicroRNAs (miRNA) are small non-coding RNAs that negatively regulate gene expression in a sequence- specific manner. Post-transcriptional silencing of target genes by miRNA occurs either by specific cleavage of homologous mRNA or by specific inhibition of protein synthesis. MiRNAs are essential regulators of various processes such as proliferation, differentiation, development, cell death and interaction between virus and host cell. AIM: The aim of this paper is to summarize the main findings from research on miRNA biogenesis, functionality and cancer relevance. METHOD: A narrative literature review of all of the relevant papers known to the authors was conducted. RESULTS: Several human diseases including cancer are associated with aberrant regulation of miRNAs expression or deficiency in miRNA biogenesis. Analysis of miRNA expression signatures can serve as a valuable tool for cancer classification, diagnostics and prediction of tumor behavior. CONCLUSIONS: There has been demonstrated a possibility to use these microRNA signatures for a specific cancer classification with potential predictive and therapeutic value. The known data provide evidence that microRNAs may open new ways for cancer diagnosis, prognosis estimation and therapy.
Cieľ: V rámci prevencie CAN syndrómu u detí sme sa v práci zamerali na posúdenie funkčnosti rodín a vplyvu rizikových faktorov u detí z ambulancií a sociálnych zariadení. Metódy: Pre zber empirických údajov sme použili dotazník funkčnosti rodiny (DFR). Táto metóda umožňuje zistiť výslednú funkčnosť rodiny a ako sa na nej podieľajú jednotlivé diagnostické kritéria. CAN syndróm sa najčastejšie odohráva v nefunkčných rodinách, ktoré podľa závažnosti delíme na problémové, dysfunkčné a afunkčné. Súbor tvorilo 795 detí vo veku 0-6 rokov. Výsledky: Nefunkčných rodín v súbore detí z ambulancií bolo 19,8% a v súbore detí zo sociálnych zariadení 99 %. Najdôležitejším rizikovým faktorom vo vzťahu k funkčnosti rodín v obidvoch súboroch sa preukázal emocionálny faktor. U detí z ambulancií bol rovnako významný aj sociálno-ekonomický faktor, ktorý u detí zo sociálnych zariadení sa preukázal ako menej významný. Ďalším dôležitým faktorom vo vzťahu k funkčnosti rodiny bol v obidvoch súboroch zdravotný stav a vývin dieťaťa. Závery: Funkčnosť rodiny môže byť najlepším ukazovateľom rizika týrania, zneužívania a zanedbávania dieťaťa (CAN syndrómu). Úlohou ošetrovateľstva je zamerať sa práve na identifikáciu jeho potencionálnych rizikových faktorov a realizáciu preventívnych opatrení.
Aim: Within prevention CAN syndrome on children, we focused on the appraisal of family functionality and the influence of risk factors on children from the outpatient departments and sanitary facilities. Methods: To gain the empirical data, we used the questionnaire of family functionality (QFF). This method enabled us to determine resulting family functionality and share of particular diagnostic criteria. CAN syndrome is most frequently taken place in the non-functional families, which can be divided by importance to problem once, dysfunction once and afunction once. The data were formed by 795 children in the age of 0-6 years. Results: There were 19,8 % of non-functional families in the complex of children from outpatient departments and 99 % in the complex of children from the sanitary facilities. The emotional factor was the most important risk factor in the relation to non-functionality of families in both complexes. Concerning children from outpatient departments, social-economic factor was the same importance, but concerning children from sanitary facilities, this attribute was proved as less important. In the relation to a family functionality, the next important factor in both complexes was the health state and the child evolution. Conclusions: The functionality of family could be the best indicator of risk of torture, abuse, and neglect of child (CAN syndrome). The function of nursing is to focus on the identification of its potentional risk factors and the realization of preventive precautions.
- MeSH
- dítě MeSH
- dospělí MeSH
- interpretace statistických dat MeSH
- kojenec MeSH
- lidé MeSH
- ošetřovatelství v péči o matku a dítě metody pracovní síly MeSH
- předškolní dítě MeSH
- primární prevence metody statistika a číselné údaje MeSH
- rizikové faktory MeSH
- rodina psychologie MeSH
- rodinné vztahy MeSH
- zneužívané dítě prevence a kontrola statistika a číselné údaje MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
Telomere shortening at chromosomal ends due to the constraints of the DNA replication process acts as a tumor suppressor by restricting the replicative potential in primary cells. Cancers evade that limitation primarily through the reactivation of telomerase via different mechanisms. Mutations within the promoter of the telomerase reverse transcriptase (TERT) gene represent a definite mechanism for the ribonucleic enzyme regeneration predominantly in cancers that arise from tissues with low rates of self-renewal. The promoter mutations cause a moderate increase in TERT transcription and consequent telomerase upregulation to the levels sufficient to delay replicative senescence but not prevent bulk telomere shortening and genomic instability. Since the discovery, a staggering number of studies have resolved the discrete aspects, effects and clinical relevance of the TERT promoter mutations. The promoter mutations link transcription of TERT with oncogenic pathways, associate with markers of poor outcome and define patients with reduced survivals in several cancers. In this review, we discuss the occurrence and impact of the promoter mutations and highlight the mechanism of TERT activation. We further deliberate on the foundational question of the abundance of the TERT promoter mutations and a general dearth of functional mutations within noncoding sequences, as evident from pan-cancer analysis of the whole-genomes. We posit that the favorable genomic constellation within the TERT promoter may be less than a common occurrence in other noncoding functional elements. Besides, the evolutionary constraints limit the functional fraction within the human genome, hence the lack of abundant mutations outside the coding sequences.
- MeSH
- aktivace transkripce MeSH
- lidé MeSH
- mutace * MeSH
- nádory klasifikace genetika patologie MeSH
- nestabilita genomu MeSH
- promotorové oblasti (genetika) * MeSH
- stárnutí buněk MeSH
- telomerasa genetika metabolismus MeSH
- telomery genetika MeSH
- zkracování telomer MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity.Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.
- MeSH
- absentérství * MeSH
- antidepresiva terapeutické užití MeSH
- deprese terapie MeSH
- lidé MeSH
- pracovní neschopnost * MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hepatic in vitro models that accurately replicate phenotypes and functionality of the human liver are needed for applications in toxicology, pharmacology and biomedicine. Notably, it has become clear that liver function can only be sustained in 3D culture systems at physiologically relevant cell densities. Additionally, drug metabolism and drug-induced cellular toxicity often follow distinct spatial micropatterns of the metabolic zones in the liver acinus, calling for models that capture this zonation. We demonstrate the manufacture of accurate liver microphysiological systems (MPS) via engineering of 3D stereolithography printed hydrogel chips with arrays of diffusion open synthetic vasculature channels at spacings approaching in vivo capillary distances. Chip designs are compatible with seeding of cell suspensions or preformed liver cell spheroids. Importantly, primary human hepatocytes (PHH) and hiPSC-derived hepatocyte-like cells remain viable, exhibit improved molecular phenotypes compared to isogenic monolayer and static spheroid cultures and form interconnected tissue structures over the course of multiple weeks in perfused culture. 3D optical oxygen mapping of embedded sensor beads shows that the liver MPS recapitulates oxygen gradients found in the acini, which translates into zone-specific acet-ami-no-phen toxicity patterns. Zonation, here naturally generated by high cell densities and associated oxygen and nutrient utilization along the flow path, is also documented by spatial proteomics showing increased concentration of periportal- versus perivenous-associated proteins at the inlet region and vice versa at the outlet region. The presented microperfused liver MPS provides a promising platform for the mesoscale culture of human liver cells at phenotypically relevant densities and oxygen exposures. STATEMENT OF SIGNIFICANCE: A full 3D tissue culture platform is presented, enabled by massively parallel arrays of high-resolution 3D printed microperfusion hydrogel channels that functionally mimics tissue vasculature. The platform supports long-term culture of liver models with dimensions of several millimeters at physiologically relevant cell densities, which is difficult to achieve with other methods. Human liver models are generated from seeded primary human hepatocytes (PHHs) cultured for two weeks, and from seeded spheroids of hiPSC-derived human liver-like cells cultured for two months. Both model types show improved functionality over state-of-the-art 3D spheroid suspensions cultured in parallel. The platform can generate physiologically relevant oxygen gradients driven by consumption rather than supply, which was validated by visualization of embedded oxygen-sensitive microbeads, which is exploited to demonstrate zonation-specific toxicity in PHH liver models.
- MeSH
- hepatocyty * metabolismus MeSH
- hydrogely metabolismus MeSH
- játra * MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
